In a series of experiments the prolonged feeding of rats with thioacetamide and 4-dimethylaminoazobenzene provoked an increase in mitochondrial calcium. It seems likely that this continuous mitochondrial overloading with Ca2+ is related to metabolic and functional changes of the liver cell leading to a neoplastic transformation. The drastic changes in cell membrane permeability of cholangiocarcinoma tumor cells, reflected by an increased concentration of extracellular cations (calcium and sodium), while the intracellular cations tended to decrease, indicate that the mitochondrial function of specification of cell membrane characteristics is possibly impaired by that calcification.
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References
1.
AnghileriL. J.: Metabolism of acid mucopolysaccharides in hepatoma and in normal liver. Oncology, 30: 304–317, 1974.
2.
AnghileriL. J.: On the similarity of alkaline earths metabolism and 67Ga accumulation by liver as revealed by acute thioacetamide intoxication. J. Nucl. Biol. Med., 19: 145–148, 1975.
3.
AnghileriL. J.: Metabolism of calcium and magnesium in liver during acute thioacetamide intoxication. Int. J. Clin. Pharmacol., 14: 101–108, 1976.
4.
AnghileriL. J., HeidbrederM., WeilerG., DermietzelR.: Liver tumors induced by 4-dimethylaminoazobenzene. Experimental basis for a chemical carcinogenesis concept. Arch. Geschwülstforsch., 46: 639–656, 1976.
5.
BaumH.: Possible role of mitochondria in oncogenesis. Lancet, 2: 738–739, 1973.
6.
ChanceB., MelaL.: Intramitochondrial pH changes in cation accumulation. Proc. Nat. Acad. Sci. USA, 55: 1243–1245, 1966.
7.
CináflJ., SprinciJ. L., KourilekM.: Calcification of cell nuclei in experimental necrosis in vivo. Nature, 216: 1010–1011, 1967.
8.
ConeC. D.Jr.: Unified theory on the basic mechanism of normal mitotic control and oncogenesis. J. Theor. Biol., 30: 151–181, 1971.
9.
GrantH. C., ReesK. R.: The precancerous liver; correlations of histological and biochemical changes in rats during prolonged administration of thioacetamide and « butter yellow ». Proc. Roy. Soc. (Biol.), 148: 117–136, 1958.
10.
GuptaD. N.: Nodular cirrhosis and metastasising tumors produced in the liver of rats by prolonged feeding with thioacetamide. J. Path. Bact., 72: 415–426, 1956.
11.
HeidcampW. H., KarasakiS.: Intracellular cations and basophilia in rat liver parenchyma during azo dye carcinogenesis. Cancer Res., 36: 3086–3093, 1976.
12.
KratzingC. C., DunstoneJ. R., MadsenN. P., MacDonaldP., BellH.: Variations in rat liver calcium and magnesium. Biochem. Pharmacol., 3: 272–276, 1960.
13.
KroegerH., TroschW., MullerG.: Changes in nuclear electrolytes of Chironomus thummi salivary gland cells during development. Exp. Cell Res., 80: 329–339, 1973.
14.
LowryO. H., RosebroughN. J., FarrA. L., RandallR. J.: Protein measurement with Folin phenol reagent. J. Biol. Chem., 193: 265–268, 1951.
15.
ReynoldsE. S.: Liver parenchymal cell injury. I. Initial alterations of the cell following poisoning with carbon tetrachloride. J. Cell Biol., 19: 139–157, 1963.
16.
StriebichM. J., SheltonE., SchneiderW. C.: Quantitative morphological studies on the livers and liver homogenates of rats fed 2-methyl- or 3′-methyl-4-dimethylaminoazobenzene. Cancer Res., 13: 279–284, 1953.
17.
WarburgO.: On the origin of cancer cells. Science, 123: 309–311, 1956.
18.
WhiteM. T., TewariK. K.: Structural and functional changes in Novikoff hepatoma mitochondria. Cancer Res., 33: 1645–1653, 1973.
